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Protein

Hamartin

Gene

TSC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling.2 Publications

GO - Molecular functioni

  • chaperone binding Source: UniProtKB
  • GTPase regulator activity Source: GO_Central
  • protein N-terminus binding Source: UniProtKB

GO - Biological processi

  • activation of GTPase activity Source: UniProtKB
  • adaptive immune response Source: Ensembl
  • adult locomotory behavior Source: ParkinsonsUK-UCL
  • cardiac muscle cell differentiation Source: Ensembl
  • cell cycle arrest Source: Reactome
  • cell-matrix adhesion Source: UniProtKB
  • cell projection organization Source: Ensembl
  • cellular response to oxygen-glucose deprivation Source: ParkinsonsUK-UCL
  • cerebral cortex development Source: Ensembl
  • glucose import Source: Ensembl
  • hippocampus development Source: Ensembl
  • kidney development Source: Ensembl
  • memory T cell differentiation Source: Ensembl
  • myelination Source: Ensembl
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cell size Source: Ensembl
  • negative regulation of insulin receptor signaling pathway Source: GO_Central
  • negative regulation of macroautophagy Source: ParkinsonsUK-UCL
  • negative regulation of TOR signaling Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • neural tube closure Source: Ensembl
  • positive regulation of focal adhesion assembly Source: UniProtKB
  • potassium ion transport Source: Ensembl
  • protein heterooligomerization Source: Ensembl
  • protein stabilization Source: UniProtKB
  • regulation of cell cycle Source: GO_Central
  • regulation of cell-matrix adhesion Source: UniProtKB
  • regulation of neuron death Source: ParkinsonsUK-UCL
  • regulation of phosphoprotein phosphatase activity Source: UniProtKB
  • regulation of protein kinase activity Source: Ensembl
  • regulation of stress fiber assembly Source: UniProtKB
  • regulation of translation Source: UniProtKB
  • response to insulin Source: UniProtKB
  • rRNA export from nucleus Source: UniProtKB
  • synapse organization Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165699-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165181. Inhibition of TSC complex formation by PKB.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
SignaLinkiQ92574.
SIGNORiQ92574.

Names & Taxonomyi

Protein namesi
Recommended name:
Hamartin
Alternative name(s):
Tuberous sclerosis 1 protein
Gene namesi
Name:TSC1
Synonyms:KIAA0243, TSC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:12362. TSC1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Membrane 1 Publication; Peripheral membrane protein 1 Publication

  • Note: At steady state found in association with membranes.

GO - Cellular componenti

  • cell cortex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: Ensembl
  • cytosol Source: UniProtKB
  • growth cone Source: Ensembl
  • lamellipodium Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleus Source: ParkinsonsUK-UCL
  • perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
  • plasma membrane Source: HPA
  • protein complex Source: UniProtKB
  • TSC1-TSC2 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Tuberous sclerosis 1 (TSC1)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes.
See also OMIM:191100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00939751E → D in TSC1; unknown pathological significance. Corresponds to variant rs118203342dbSNPEnsembl.1
Natural variantiVAR_07063661L → R in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203345dbSNPEnsembl.1
Natural variantiVAR_05438772L → P in TSC1. 1 PublicationCorresponds to variant rs118203354dbSNPEnsembl.1
Natural variantiVAR_070637117L → P in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 2 PublicationsCorresponds to variant rs118203368dbSNPEnsembl.1
Natural variantiVAR_070638126V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514843dbSNPEnsembl.1
Natural variantiVAR_070639128Missing in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_070640132G → D in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514784dbSNPEnsembl.1
Natural variantiVAR_070641133V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203381dbSNPEnsembl.1
Natural variantiVAR_070643180L → P in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203396dbSNPEnsembl.1
Natural variantiVAR_009399191L → H in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203403dbSNPEnsembl.1
Natural variantiVAR_009400198 – 199NF → I in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 1 Publication2
Natural variantiVAR_009401224M → R in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203426dbSNPEnsembl.1
Natural variantiVAR_070645246R → K in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203436dbSNPEnsembl.1
Natural variantiVAR_070646305G → R in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203468dbSNPEnsembl.1
Natural variantiVAR_070647305G → W in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203468dbSNPEnsembl.1
Natural variantiVAR_070648336R → Q in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514808dbSNPEnsembl.1
Natural variantiVAR_070649362P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514864dbSNPEnsembl.1
Natural variantiVAR_070650411L → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514840dbSNPEnsembl.1
Natural variantiVAR_009403417T → I in TSC1; unknown pathological significance; does not affect interaction with TSC2. 3 PublicationsCorresponds to variant rs77464996dbSNPEnsembl.1
Natural variantiVAR_070651448P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203518dbSNPEnsembl.1
Natural variantiVAR_054391500R → Q in TSC1. 1 PublicationCorresponds to variant rs118203538dbSNPEnsembl.1
Natural variantiVAR_070653523A → P in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203548dbSNPEnsembl.1
Natural variantiVAR_070654567A → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514880dbSNPEnsembl.1
Natural variantiVAR_009405586 – 589CKIP → S in TSC1. 4
Natural variantiVAR_009407654Q → E in TSC1. 1 PublicationCorresponds to variant rs75820036dbSNPEnsembl.1
Natural variantiVAR_070655693D → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514800dbSNPEnsembl.1
Natural variantiVAR_070656698L → R in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514802dbSNPEnsembl.1
Natural variantiVAR_070657701Q → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203639dbSNPEnsembl.1
Natural variantiVAR_009408726A → E in TSC1. 1 PublicationCorresponds to variant rs118203655dbSNPEnsembl.1
Natural variantiVAR_070658762N → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203670dbSNPEnsembl.1
Natural variantiVAR_070659811R → G in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514814dbSNPEnsembl.1
Natural variantiVAR_070660883A → T in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203721dbSNPEnsembl.1
Natural variantiVAR_009412899T → S in TSC1. 1 PublicationCorresponds to variant rs76801599dbSNPEnsembl.1
Natural variantiVAR_070661978L → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514859dbSNPEnsembl.1
Natural variantiVAR_0706621043Missing in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_0706641146D → Y in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514806dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Tumor suppressor

Organism-specific databases

DisGeNETi7248.
MalaCardsiTSC1.
MIMi191100. phenotype.
OpenTargetsiENSG00000165699.
Orphaneti269008. Isolated focal cortical dysplasia type IIb.
538. Lymphangioleiomyomatosis.
805. Tuberous sclerosis.
PharmGKBiPA37034.

Polymorphism and mutation databases

BioMutaiTSC1.
DMDMi9297077.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656511 – 1164HamartinAdd BLAST1164

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei487PhosphoserineCombined sources1
Modified residuei505PhosphoserineCombined sources1 Publication1
Modified residuei511PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1
Modified residuei598PhosphoserineCombined sources1
Modified residuei1100PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-505 does not affect interaction with TSC2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92574.
PaxDbiQ92574.
PeptideAtlasiQ92574.
PRIDEiQ92574.

PTM databases

iPTMnetiQ92574.
PhosphoSitePlusiQ92574.

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.

Gene expression databases

BgeeiENSG00000165699.
CleanExiHS_TSC1.
ExpressionAtlasiQ92574. baseline and differential.
GenevisibleiQ92574. HS.

Organism-specific databases

HPAiCAB011568.
CAB012481.
HPA048549.

Interactioni

Subunit structurei

Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with DOCK7. Interacts with FBXW5 and TBC1D7.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BEX3Q009945EBI-1047085,EBI-741753
IKBKBO149203EBI-1047085,EBI-81266
MAPK14Q165392EBI-1047085,EBI-73946
TSC2P4981510EBI-1047085,EBI-396587

GO - Molecular functioni

  • chaperone binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113099. 47 interactors.
IntActiQ92574. 42 interactors.
MINTiMINT-1534928.
STRINGi9606.ENSP00000298552.

Structurei

Secondary structure

11164
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi941 – 971Combined sources31
Helixi975 – 991Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4Z6YX-ray2.81C/D/F/H938-993[»]
5EJCX-ray3.10C/D/E/F939-992[»]
ProteinModelPortaliQ92574.
SMRiQ92574.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili721 – 997Sequence analysisAdd BLAST277

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1034 – 1037Poly-Gly4
Compositional biasi1038 – 1043Poly-Ser6

Domaini

The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IG36. Eukaryota.
ENOG411020J. LUCA.
GeneTreeiENSGT00390000014148.
HOGENOMiHOG000232119.
HOVERGENiHBG012559.
InParanoidiQ92574.
KOiK07206.
OMAiPKQAFTP.
OrthoDBiEOG091G01O5.
PhylomeDBiQ92574.
TreeFamiTF325466.

Family and domain databases

InterProiIPR007483. Hamartin.
[Graphical view]
PANTHERiPTHR15154. PTHR15154. 1 hit.
PfamiPF04388. Hamartin. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92574-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL
60 70 80 90 100
ETSSQPALHI LTTLQEPHDK HLLDRINEYV GKAATRLSIL SLLGHVIRLQ
110 120 130 140 150
PSWKHKLSQA PLLPSLLKCL KMDTDVVVLT TGVLVLITML PMIPQSGKQH
160 170 180 190 200
LLDFFDIFGR LSSWCLKKPG HVAEVYLVHL HASVYALFHR LYGMYPCNFV
210 220 230 240 250
SFLRSHYSMK ENLETFEEVV KPMMEHVRIH PELVTGSKDH ELDPRRWKRL
260 270 280 290 300
ETHDVVIECA KISLDPTEAS YEDGYSVSHQ ISARFPHRSA DVTTSPYADT
310 320 330 340 350
QNSYGCATST PYSTSRLMLL NMPGQLPQTL SSPSTRLITE PPQATLWSPS
360 370 380 390 400
MVCGMTTPPT SPGNVPPDLS HPYSKVFGTT AGGKGTPLGT PATSPPPAPL
410 420 430 440 450
CHSDDYVHIS LPQATVTPPR KEERMDSARP CLHRQHHLLN DRGSEEPPGS
460 470 480 490 500
KGSVTLSDLP GFLGDLASEE DSIEKDKEEA AISRELSEIT TAEAEPVVPR
510 520 530 540 550
GGFDSPFYRD SLPGSQRKTH SAASSSQGAS VNPEPLHSSL DKLGPDTPKQ
560 570 580 590 600
AFTPIDLPCG SADESPAGDR ECQTSLETSI FTPSPCKIPP PTRVGFGSGQ
610 620 630 640 650
PPPYDHLFEV ALPKTAHHFV IRKTEELLKK AKGNTEEDGV PSTSPMEVLD
660 670 680 690 700
RLIQQGADAH SKELNKLPLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN
710 720 730 740 750
QLLYERFKRQ QHALRNRRLL RKVIKAAALE EHNAAMKDQL KLQEKDIQMW
760 770 780 790 800
KVSLQKEQAR YNQLQEQRDT MVTKLHSQIR QLQHDREEFY NQSQELQTKL
810 820 830 840 850
EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES VQQQMEFLNR
860 870 880 890 900
QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELEK NRSHVLQQTQ
910 920 930 940 950
RLDTSQKRIL ELESHLAKKD HLLLEQKKYL EDVKLQARGQ LQAAESRYEA
960 970 980 990 1000
QKRITQVFEL EILDLYGRLE KDGLLKKLEE EKAEAAEAAE ERLDCCNDGC
1010 1020 1030 1040 1050
SDSMVGHNEE ASGHNGETKT PRPSSARGSS GSRGGGGSSS SSSELSTPEK
1060 1070 1080 1090 1100
PPHQRAGPFS SRWETTMGEA SASIPTTVGS LPSSKSFLGM KARELFRNKS
1110 1120 1130 1140 1150
ESQCDEDGMT SSLSESLKTE LGKDLGVEAK IPLNLDGPHP SPPTPDSVGQ
1160
LHIMDYNETH HEHS
Length:1,164
Mass (Da):129,767
Last modified:November 1, 1998 - v2
Checksum:iEF15509385C7AACC
GO
Isoform 2 (identifier: Q92574-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-120: Missing.

Note: No experimental confirmation available.
Show »
Length:1,113
Mass (Da):124,015
Checksum:i6EA012443870A73C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00939751E → D in TSC1; unknown pathological significance. Corresponds to variant rs118203342dbSNPEnsembl.1
Natural variantiVAR_07063661L → R in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203345dbSNPEnsembl.1
Natural variantiVAR_05438668H → R in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. 1 PublicationCorresponds to variant rs118203347dbSNPEnsembl.1
Natural variantiVAR_05438772L → P in TSC1. 1 PublicationCorresponds to variant rs118203354dbSNPEnsembl.1
Natural variantiVAR_070637117L → P in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 2 PublicationsCorresponds to variant rs118203368dbSNPEnsembl.1
Natural variantiVAR_070638126V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514843dbSNPEnsembl.1
Natural variantiVAR_070639128Missing in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_070640132G → D in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514784dbSNPEnsembl.1
Natural variantiVAR_070641133V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203381dbSNPEnsembl.1
Natural variantiVAR_054388158F → C in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. 1 PublicationCorresponds to variant rs118203385dbSNPEnsembl.1
Natural variantiVAR_070642158F → S Found in a patient suspected of having tuberous sclerosis; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203385dbSNPEnsembl.1
Natural variantiVAR_070643180L → P in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203396dbSNPEnsembl.1
Natural variantiVAR_009398190R → S.1
Natural variantiVAR_009399191L → H in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203403dbSNPEnsembl.1
Natural variantiVAR_009400198 – 199NF → I in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 1 Publication2
Natural variantiVAR_070644204R → P Found in a patient suspected of having tuberous sclerosis; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514834dbSNPEnsembl.1
Natural variantiVAR_054389206H → D in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. 1 Publication1
Natural variantiVAR_054390216F → L in a bladder tumor; diffuse punctate cytoplasmic distribution in aminoacid-starved conditions; does not affect interaction with TSC2. 1 Publication1
Natural variantiVAR_009401224M → R in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203426dbSNPEnsembl.1
Natural variantiVAR_070645246R → K in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203436dbSNPEnsembl.1
Natural variantiVAR_070646305G → R in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203468dbSNPEnsembl.1
Natural variantiVAR_070647305G → W in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203468dbSNPEnsembl.1
Natural variantiVAR_009402322M → T.5 PublicationsCorresponds to variant rs1073123dbSNPEnsembl.1
Natural variantiVAR_070648336R → Q in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514808dbSNPEnsembl.1
Natural variantiVAR_070649362P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514864dbSNPEnsembl.1
Natural variantiVAR_070650411L → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514840dbSNPEnsembl.1
Natural variantiVAR_009403417T → I in TSC1; unknown pathological significance; does not affect interaction with TSC2. 3 PublicationsCorresponds to variant rs77464996dbSNPEnsembl.1
Natural variantiVAR_070651448P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203518dbSNPEnsembl.1
Natural variantiVAR_054391500R → Q in TSC1. 1 PublicationCorresponds to variant rs118203538dbSNPEnsembl.1
Natural variantiVAR_070652509R → Q Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203543dbSNPEnsembl.1
Natural variantiVAR_070653523A → P in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203548dbSNPEnsembl.1
Natural variantiVAR_070654567A → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514880dbSNPEnsembl.1
Natural variantiVAR_009404577E → D.1 PublicationCorresponds to variant rs118203571dbSNPEnsembl.1
Natural variantiVAR_009405586 – 589CKIP → S in TSC1. 4
Natural variantiVAR_009406587K → R.2 PublicationsCorresponds to variant rs118203576dbSNPEnsembl.1
Natural variantiVAR_009407654Q → E in TSC1. 1 PublicationCorresponds to variant rs75820036dbSNPEnsembl.1
Natural variantiVAR_070655693D → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514800dbSNPEnsembl.1
Natural variantiVAR_070656698L → R in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514802dbSNPEnsembl.1
Natural variantiVAR_070657701Q → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203639dbSNPEnsembl.1
Natural variantiVAR_009408726A → E in TSC1. 1 PublicationCorresponds to variant rs118203655dbSNPEnsembl.1
Natural variantiVAR_009409732H → Y Rare polymorphism; might be associated with susceptibility to focal cortical dysplasia of the Taylor balloon cell type. 4 PublicationsCorresponds to variant rs118203657dbSNPEnsembl.1
Natural variantiVAR_070658762N → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203670dbSNPEnsembl.1
Natural variantiVAR_009410809E → Q.1 PublicationCorresponds to variant rs118203692dbSNPEnsembl.1
Natural variantiVAR_070659811R → G in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514814dbSNPEnsembl.1
Natural variantiVAR_009411829S → R.1 PublicationCorresponds to variant rs118203699dbSNPEnsembl.1
Natural variantiVAR_070660883A → T in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203721dbSNPEnsembl.1
Natural variantiVAR_009412899T → S in TSC1. 1 PublicationCorresponds to variant rs76801599dbSNPEnsembl.1
Natural variantiVAR_070661978L → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514859dbSNPEnsembl.1
Natural variantiVAR_0094131035G → S Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. 3 PublicationsCorresponds to variant rs118203742dbSNPEnsembl.1
Natural variantiVAR_0706621043Missing in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_0706631097R → H Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs118203750dbSNPEnsembl.1
Natural variantiVAR_0094141108G → S.1 PublicationCorresponds to variant rs118203753dbSNPEnsembl.1
Natural variantiVAR_0706641146D → Y in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant rs397514806dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04289070 – 120Missing in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013168 mRNA. Translation: AAC51674.1.
AK303030 mRNA. Translation: BAH13883.1.
AL445645 Genomic DNA. Translation: CAH72112.1.
CH471090 Genomic DNA. Translation: EAW88021.1.
AC002096 Genomic DNA. No translation available.
D87683 mRNA. Translation: BAA13436.1.
AF234185 Genomic DNA. Translation: AAF61948.1.
CCDSiCCDS55350.1. [Q92574-2]
CCDS6956.1. [Q92574-1]
PIRiT03814.
RefSeqiNP_000359.1. NM_000368.4. [Q92574-1]
NP_001155898.1. NM_001162426.1.
NP_001155899.1. NM_001162427.1. [Q92574-2]
XP_005272268.1. XM_005272211.1. [Q92574-1]
XP_006717334.1. XM_006717271.1. [Q92574-1]
XP_011517281.1. XM_011518979.2. [Q92574-1]
XP_016870585.1. XM_017015096.1. [Q92574-1]
XP_016870586.1. XM_017015097.1. [Q92574-1]
UniGeneiHs.370854.

Genome annotation databases

EnsembliENST00000298552; ENSP00000298552; ENSG00000165699. [Q92574-1]
ENST00000440111; ENSP00000394524; ENSG00000165699. [Q92574-1]
ENST00000545250; ENSP00000444017; ENSG00000165699. [Q92574-2]
GeneIDi7248.
KEGGihsa:7248.
UCSCiuc064wss.1. human. [Q92574-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Tuberous sclerosis database Tuberous sclerosis 1 (TSC1)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013168 mRNA. Translation: AAC51674.1.
AK303030 mRNA. Translation: BAH13883.1.
AL445645 Genomic DNA. Translation: CAH72112.1.
CH471090 Genomic DNA. Translation: EAW88021.1.
AC002096 Genomic DNA. No translation available.
D87683 mRNA. Translation: BAA13436.1.
AF234185 Genomic DNA. Translation: AAF61948.1.
CCDSiCCDS55350.1. [Q92574-2]
CCDS6956.1. [Q92574-1]
PIRiT03814.
RefSeqiNP_000359.1. NM_000368.4. [Q92574-1]
NP_001155898.1. NM_001162426.1.
NP_001155899.1. NM_001162427.1. [Q92574-2]
XP_005272268.1. XM_005272211.1. [Q92574-1]
XP_006717334.1. XM_006717271.1. [Q92574-1]
XP_011517281.1. XM_011518979.2. [Q92574-1]
XP_016870585.1. XM_017015096.1. [Q92574-1]
XP_016870586.1. XM_017015097.1. [Q92574-1]
UniGeneiHs.370854.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4Z6YX-ray2.81C/D/F/H938-993[»]
5EJCX-ray3.10C/D/E/F939-992[»]
ProteinModelPortaliQ92574.
SMRiQ92574.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113099. 47 interactors.
IntActiQ92574. 42 interactors.
MINTiMINT-1534928.
STRINGi9606.ENSP00000298552.

PTM databases

iPTMnetiQ92574.
PhosphoSitePlusiQ92574.

Polymorphism and mutation databases

BioMutaiTSC1.
DMDMi9297077.

Proteomic databases

EPDiQ92574.
PaxDbiQ92574.
PeptideAtlasiQ92574.
PRIDEiQ92574.

Protocols and materials databases

DNASUi7248.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000298552; ENSP00000298552; ENSG00000165699. [Q92574-1]
ENST00000440111; ENSP00000394524; ENSG00000165699. [Q92574-1]
ENST00000545250; ENSP00000444017; ENSG00000165699. [Q92574-2]
GeneIDi7248.
KEGGihsa:7248.
UCSCiuc064wss.1. human. [Q92574-1]

Organism-specific databases

CTDi7248.
DisGeNETi7248.
GeneCardsiTSC1.
GeneReviewsiTSC1.
HGNCiHGNC:12362. TSC1.
HPAiCAB011568.
CAB012481.
HPA048549.
MalaCardsiTSC1.
MIMi191100. phenotype.
605284. gene.
neXtProtiNX_Q92574.
OpenTargetsiENSG00000165699.
Orphaneti269008. Isolated focal cortical dysplasia type IIb.
538. Lymphangioleiomyomatosis.
805. Tuberous sclerosis.
PharmGKBiPA37034.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG36. Eukaryota.
ENOG411020J. LUCA.
GeneTreeiENSGT00390000014148.
HOGENOMiHOG000232119.
HOVERGENiHBG012559.
InParanoidiQ92574.
KOiK07206.
OMAiPKQAFTP.
OrthoDBiEOG091G01O5.
PhylomeDBiQ92574.
TreeFamiTF325466.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165699-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165181. Inhibition of TSC complex formation by PKB.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
SignaLinkiQ92574.
SIGNORiQ92574.

Miscellaneous databases

ChiTaRSiTSC1. human.
GeneWikiiTSC1.
GenomeRNAii7248.
PROiQ92574.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165699.
CleanExiHS_TSC1.
ExpressionAtlasiQ92574. baseline and differential.
GenevisibleiQ92574. HS.

Family and domain databases

InterProiIPR007483. Hamartin.
[Graphical view]
PANTHERiPTHR15154. PTHR15154. 1 hit.
PfamiPF04388. Hamartin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTSC1_HUMAN
AccessioniPrimary (citable) accession number: Q92574
Secondary accession number(s): B7Z897, Q5VVN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.